{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:42:57Z","timestamp":1791614577632,"version":"4.3.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Psychopharmacology"],"published-print":{"date-parts":[[2020,11]]},"DOI":"10.1007\/s00213-020-05629-2","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T19:02:45Z","timestamp":1596740565000},"page":"3481-3487","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: a systematic review and meta-analysis of double-blind, randomized placebo-controlled trials"],"prefix":"10.1007","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9237-2236","authenticated-orcid":false,"given":"Taro","family":"Kishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobumi","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Okuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sakuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakao","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"5629_CR1","doi-asserted-by":"publisher","unstructured":"Bauer IE, Green C, Colpo GD, Teixeira AL, Selvaraj S, Durkin K, Zunta-Soares GB, Soares JC (2018) A double-blind, randomized, placebo-controlled study of aspirin and N-acetylcysteine as adjunctive treatments for bipolar depression. J Clin Psychiatry 80(1). https:\/\/doi.org\/10.4088\/JCP.18m12200","DOI":"10.4088\/JCP.18m12200"},{"key":"5629_CR2","doi-asserted-by":"publisher","unstructured":"Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI (2008) N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial. Biol Psychiatry 64(6):468\u2013475. https:\/\/doi.org\/10.1016\/j.biopsych.2008.04.022","DOI":"10.1016\/j.biopsych.2008.04.022"},{"key":"5629_CR3","doi-asserted-by":"publisher","unstructured":"Berk M, Dean OM, Cotton SM, Gama CS, Kapczinski F, Fernandes B, Kohlmann K, Jeavons S, Hewitt K, Moss K, Allwang C, Schapkaitz I, Cobb H, Bush AI, Dodd S, Malhi GS (2012) Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial. BMC Med 10:91. https:\/\/doi.org\/10.1186\/1741-7015-10-91","DOI":"10.1186\/1741-7015-10-91"},{"key":"5629_CR4","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.tips.2013.01.001","volume":"34","author":"M Berk","year":"2013","unstructured":"Berk M, Malhi GS, Gray LJ, Dean OM (2013) The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci 34:167\u2013177","journal-title":"Trends Pharmacol Sci"},{"key":"5629_CR5","doi-asserted-by":"publisher","unstructured":"Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, Kohlmann K, Hewitt K, Moss K, Allwang C, Schapkaitz I, Robbins J, Cobb H, Ng F, Dodd S, Bush AI, Malhi GS (2014) The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry 75(6):628\u2013636. https:\/\/doi.org\/10.4088\/JCP.13m08454","DOI":"10.4088\/JCP.13m08454"},{"key":"5629_CR6","doi-asserted-by":"publisher","unstructured":"Berk M, Turner A, Malhi GS, Ng CH, Cotton SM, Dodd S, Samuni Y, Tanious M, McAulay C, Dowling N, Sarris J, Owen L, Waterdrinker A, Smith D, Dean OM (2019) A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo. BMC Med 17(1):18. https:\/\/doi.org\/10.1186\/s12916-019-1257-1","DOI":"10.1186\/s12916-019-1257-1"},{"key":"5629_CR7","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1111\/j.1601-5215.2009.00397.x","volume":"21","author":"M Bernardo","year":"2009","unstructured":"Bernardo M, Dodd S, Gama CS, Copolov DL, Dean O, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI, Berk M (2009) Effects of N-acetylcysteine on substance use in bipolar disorder: a randomised placebo-controlled clinical trial. Acta Neuropsychiatr 21:285\u2013291","journal-title":"Acta Neuropsychiatr"},{"key":"5629_CR8","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1111\/j.1440-1819.2012.02392.x","volume":"66","author":"OM Dean","year":"2012","unstructured":"Dean OM, Bush AI, Copolov DL, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Berk M (2012) Effects of N-acetyl cysteine on cognitive function in bipolar disorder. Psychiatry Clin Neurosci 66:514\u2013517","journal-title":"Psychiatry Clin Neurosci"},{"key":"5629_CR9","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","volume":"7","author":"R DerSimonian","year":"1986","unstructured":"DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177\u2013188","journal-title":"Control Clin Trials"},{"key":"5629_CR10","unstructured":"DSM Diagnostic and Statistical Manual of Mental Disorders. (n.d.) American Psychiatric Association"},{"key":"5629_CR11","doi-asserted-by":"publisher","unstructured":"Ellegaard PK, Licht RW, Nielsen RE, Dean OM, Berk M, Poulsen HE, Mohebbi M, Nielsen CT (2019) The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study. J Affect Disord 245:1043\u20131051. https:\/\/doi.org\/10.1016\/j.jad.2018.10.083","DOI":"10.1016\/j.jad.2018.10.083"},{"key":"5629_CR12","first-page":"321","volume":"29","author":"J Endicott","year":"1993","unstructured":"Endicott J, Nee J, Harrison W, Blumenthal R (1993) Quality of life enjoyment and satisfaction questionnaire: a new measure. Psychopharmacol Bull 29:321\u2013326","journal-title":"Psychopharmacol Bull"},{"key":"5629_CR13","doi-asserted-by":"publisher","first-page":"e457","DOI":"10.4088\/JCP.15r09984","volume":"77","author":"BS Fernandes","year":"2016","unstructured":"Fernandes BS, Dean OM, Dodd S, Malhi GS, Berk M (2016) N-acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry 77:e457\u2013e466","journal-title":"J Clin Psychiatry"},{"key":"5629_CR14","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1176\/ajp.149.8.1119-a","volume":"149","author":"HH Goldman","year":"1992","unstructured":"Goldman HH, Skodol AE, Lave TR (1992) Revising axis V for DSM-IV: a review of measures of social functioning. Am J Psychiatry 149:1148\u20131156","journal-title":"Am J Psychiatry"},{"key":"5629_CR15","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1016\/S0140-6736(15)00241-X","volume":"387","author":"I Grande","year":"2016","unstructured":"Grande I, Berk M, Birmaher B, Vieta E (2016) Bipolar disorder. Lancet 387:1561\u20131572","journal-title":"Lancet"},{"key":"5629_CR16","unstructured":"Guy W, Bonato RR (1970) Manual for the ECDEU assessment battery, 2nd ed. Chevy Chase, Md, National Institute of Mental Health"},{"key":"5629_CR17","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","volume":"32","author":"M Hamilton","year":"1959","unstructured":"Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50\u201355","journal-title":"Br J Med Psychol"},{"key":"5629_CR18","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","volume":"23","author":"M Hamilton","year":"1960","unstructured":"Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56\u201362","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"5629_CR19","doi-asserted-by":"crossref","unstructured":"Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, Welch V (2019) Cochrane handbook for systematic reviews of interventions version 6.0. wwwtrainingcochraneorg\/handbook","DOI":"10.1002\/9781119536604"},{"key":"5629_CR20","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1111\/pcn.12852","volume":"73","author":"T Kato","year":"2019","unstructured":"Kato T (2019) Current understanding of bipolar disorder: toward integration of biological basis and treatment strategies. Psychiatry Clin Neurosci 73:526\u2013540","journal-title":"Psychiatry Clin Neurosci"},{"key":"5629_CR21","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1001\/archpsyc.1987.01800180050009","volume":"44","author":"MB Keller","year":"1987","unstructured":"Keller MB, Lavori PW, Friedman B, Nielsen E, Endicott J, McDonald-Scott P, Andreasen NC (1987) The Longitudinal Interval Follow-up Evaluation. A comprehensive method for assessing outcome in prospective longitudinal studies. Arch Gen Psychiatry 44:540\u2013548","journal-title":"Arch Gen Psychiatry"},{"key":"5629_CR22","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1017\/S0033291799008570","volume":"29","author":"AC Leon","year":"1999","unstructured":"Leon AC, Solomon DA, Mueller TI, Turvey CL, Endicott J, Keller MB (1999) The Range of Impaired Functioning Tool (LIFE-RIFT): a brief measure of functional impairment. Psychol Med 29:869\u2013878","journal-title":"Psychol Med"},{"key":"5629_CR23","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.jad.2010.08.001","volume":"129","author":"PV Magalhaes","year":"2011","unstructured":"Magalhaes PV, Dean OM, Bush AI, Copolov DL, Malhi GS, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Berk M (2011) N-acetyl cysteine add-on treatment for bipolar II disorder: a subgroup analysis of a randomized placebo-controlled trial. J Affect Disord 129:317\u2013320","journal-title":"J Affect Disord"},{"key":"5629_CR24","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","volume":"392","author":"GS Malhi","year":"2018","unstructured":"Malhi GS, Mann JJ (2018) Depression. Lancet 392:2299\u20132312","journal-title":"Lancet"},{"key":"5629_CR25","doi-asserted-by":"publisher","first-page":"b2535","DOI":"10.1136\/bmj.b2535","volume":"339","author":"D Moher","year":"2009","unstructured":"Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Bmj 339:b2535","journal-title":"Bmj"},{"key":"5629_CR26","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1192\/bjp.134.4.382","volume":"134","author":"SA Montgomery","year":"1979","unstructured":"Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134:382\u2013389","journal-title":"Br J Psychiatry"},{"key":"5629_CR27","doi-asserted-by":"publisher","unstructured":"Porcu M, Urbano MR, Verri WA Jr, Barbosa DS, Baracat M, Vargas HO, Machado R, Pescim RR, Nunes SOV (2018) Effects of adjunctive N-acetylcysteine on depressive symptoms: Modulation by baseline high-sensitivity C-reactive protein. Psychiatry Res 263:268\u2013274. https:\/\/doi.org\/10.1016\/j.psychres.2018.02.056","DOI":"10.1016\/j.psychres.2018.02.056"},{"key":"5629_CR28","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/bdi.12373","volume":"18","author":"JD Rosenblat","year":"2016","unstructured":"Rosenblat JD, Kakar R, Berk M, Kessing LV, Vinberg M, Baune BT, Mansur RB, Brietzke E, Goldstein BI, McIntyre RS (2016) Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. Bipolar Disord 18:89\u2013101","journal-title":"Bipolar Disord"},{"key":"5629_CR29","doi-asserted-by":"publisher","first-page":"2972968","DOI":"10.1155\/2020\/2972968","volume":"2020","author":"APV Visentin","year":"2020","unstructured":"Visentin APV, Colombo R, Scotton E, Fracasso DS, da Rosa AR, Branco CS, Salvador M (2020) Targeting inflammatory-mitochondrial response in major depression: current evidence and further challenges. Oxidative Med Cell Longev 2020:2972968","journal-title":"Oxidative Med Cell Longev"},{"key":"5629_CR30","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1017\/S0033291798006667","volume":"28","author":"WHO","year":"1998","unstructured":"WHO (1998a) Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL group. Psychol Med 28:551\u2013558","journal-title":"Psychol Med"},{"key":"5629_CR31","volume-title":"World Health Organisation- five well-being index","author":"WHO","year":"1998","unstructured":"WHO (1998b) World Health Organisation- five well-being index. WHO Regional Office for Europe, Copenhagen"},{"key":"5629_CR32","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1192\/bjp.133.5.429","volume":"133","author":"RC Young","year":"1978","unstructured":"Young RC, Biggs JT, Ziegler VE, Meyer DA (1978) A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry : the journal of mental science 133:429\u2013435","journal-title":"Br J Psychiatry : the journal of mental science"},{"key":"5629_CR33","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1111\/acps.12862","volume":"137","author":"W Zheng","year":"2018","unstructured":"Zheng W, Zhang QE, Cai DB, Yang XH, Qiu Y, Ungvari GS, Ng CH, Berk M, Ning YP, Xiang YT (2018) N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials. Acta Psychiatr Scand 137:391\u2013400","journal-title":"Acta Psychiatr Scand"}],"container-title":["Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-020-05629-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00213-020-05629-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-020-05629-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T23:24:17Z","timestamp":1628205857000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00213-020-05629-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,6]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["5629"],"URL":"https:\/\/doi.org\/10.1007\/s00213-020-05629-2","relation":{},"ISSN":["0033-3158","1432-2072"],"issn-type":[{"value":"0033-3158","type":"print"},{"value":"1432-2072","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,6]]},"assertion":[{"value":"25 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that there are no conflicts of interest in relation to this study. We declare the following interests within the past 3\u00a0years.Dr. Kishi has received speaker\u2019s honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, MSD, Yoshitomi, and Tanabe-Mitsubishi and has received a Health Labour Sciences Research Grant, Grant-in-Aid for Scientific Research (C), and a Fujita Health University School of Medicine research grant.Dr. Miyake has received speaker\u2019s honoraria from Dainippon Sumitomo and Meiji.Dr. Okuya has received speaker\u2019s honoraria from Meiji.Dr. Sakuma has received speaker\u2019s honoraria from Eisai, Kissei, Meiji, Otsuka, and Torii and has received a Fujita Health University School of Medicine research grant as well as a Grant-in-Aid for Young Scientists (B).Dr. Iwata has received speaker\u2019s honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer and has had research grants from Daiichi Sankyo, Dainippon Sumitomo, Meiji, and Otsuka.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}